Collaborative Research: De Novo Protein Constructs for Photosynthetic Energy Transduction

合作研究：用于光合能量转导的从头蛋白质构建体

• 批准号: 2108660
• 负责人: William DeGrado
• 金额: $ 37.5万
• 依托单位: University of California-San Francisco
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-11-01 至 2024-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2108660&HistoricalAwards=false
• 关键词: Collaborative; Research; De; Novo; Protein

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Professors Michael Therien and David Beratan of Duke University and William DeGrado of University of California-San Francisco are studying new approaches to design materials that direct, store, and release energy. Biology has developed numerous designs that carry out these functions; chemists, however, have yet to create energy harvesting, storage, and release systems from scratch that possess the sophistication of those seen in nature. Recent advances in protein design enable chemists to construct large molecules that capture and manage the flow of positive charges, negative charges, and energy. By designing protein-based materials that migrate and collect charges and energy, unique optical, electrical, and chemical functions will be realized. The experimental procedures used in this effort will (i) provide new tools to build proteins having innovative designed functions, and (ii) characterize the structures and energy storage and release functions of these proteins. This pursuit will allow graduate students and postdoctoral fellows to acquire specialized training in synthetic chemistry, protein design, protein biochemistry, modern computational methods, and techniques to monitor fast processes that move charge and energy. The protein design methods developed will be broadly applicable, and enable construction of new biologically inspired materials that carry out novel functions not seen in nature. Outreach activities of this project will introduce college and pre-college students to important new technologies, and teach skills important for future careers in science and engineering.Biological energy transduction relies on protein-cofactor assemblies that possess physico-chemical functionality that far exceeds that realized to date through molecular and macromolecular design and synthesis. This research project will be undertaken to realize such complex functionality through “design from scratch” strategies that exploit de novo proteins that bind abiological cofactors, and in the process, elucidate fundamental design principles required for photosynthetic energy transduction, storage, and release. This project takes advantage of an integrated, multi-disciplinary approach to evolve peptide-cofactor complexes that possess sophisticated electro-optic functionality, encompassing cofactor design and synthesis, advanced computational methods that provide proteins that bind these cofactors in precise, organized spatial arrangements, protein expression and characterization, state-of-the-art pump-probe transient optical methods that characterize function and reaction dynamics, and high resolution protein structure determination. Information from this study is expected to elucidate fundamental principles required for photosynthetic energy transduction, and designed proteins that possess novel electro-optical function and transduce energy via innovative pathways.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学过程的化学过程（CLP）方案的支持下，杜克大学的迈克尔·塞里安（Michael Therien）和戴维·贝拉塔（David Beratan）和加利福尼亚大学弗朗西斯科分校的威廉·德格拉多（William Degrado）正在研究设计新方法，以直接，商店和释放能源。生物学开发了许多执行这些功能的设计。但是，化学家尚未从头开始创造能量收集，存储和释放系统，这些系统具有自然界中看到的精致。蛋白质设计的最新进展使化学家能够构建大分子，以捕获和管理正电荷，负电荷和能量的流动。通过设计基于蛋白质的材料来迁移和收集电荷和能量，将实现独特的光学，电气和化学功能。这项工作中使用的实验程序将（i）提供新的工具来构建具有创新设计功能的蛋白质，并且（ii）表征这些蛋白质的结构和能源存储和释放功能。这种追求将使研究生和博士后研究员获得合成化学，蛋白质设计，蛋白质生物化学，现代计算方法和技术的专业培训，以监视移动电荷和能量的快速过程。开发的蛋白质设计方法将广泛适用，并能够构建新的具有生物学启发的材料，这些材料具有自然界中未见的新功能。该项目的推广活动将向大学和大学前的学生介绍重要的新技术，并将教学技能对科学和工程领域的未来职业很重要。生物学能量翻译依赖于具有物理化学功能的蛋白质型能量组件，这些蛋白质 - 配合机构具有远远超过通过分子和大分子分子和大分子的设计和合成所实现的物理化学功能。研究项目将通过“从头开始”策略实现这种复杂的功能，从而利用从头开始的蛋白质结合了物质辅助因子，并且在此过程中，阐明了光合作用能量翻译，存储，存储和释放所需的基本设计原理。 This project takes advantage of an integrated, multi-disciplinary approach to evolve peptide-cofactor complexes that possesses sophisticated electro-optic functionality, encompassing cofactor design and synthesis, advanced computational methods that provide proteins that bind these cofactors in precise, organized spatial arrangements, protein expression and characterization, state-of-the-art pump-probe transient optical methods that characterize function and reaction dynamics, and high分辨率蛋白质结构测定。这项研究的信息有望阐明光合能翻译所需的基本原理，并设计了具有新颖的电光功能并通过创新途径传递能量的蛋白质。该奖项反映了NSF的法定任务，并通过使用该基金会的知识分子和更广泛的影响来评估NSF的法定任务，并被视为珍贵的支持。